Step 0 Eligibility: **Check for eligibility to EAQ152 COMET Step 1**
Please note: it is estimated to take 6-8 weeks to be assigned to a treatment on this trial.
-Patients must have histologically documented solid tumors or histologically confirmed diagnosis of lymphoma or multiple myeloma that has progressed following at least one line of standard systemic therapy and/or for whose disease no standard treatment exists that has been shown to prolong survival.
-Patients must have measurable disease.
-Patients must meet one of the following:
--have tumor amenable to image guided or direct vision biopsy and be willing and able to undergo a tumor biopsy for molecular profiling. Biopsy must not be considered to be more than minimal risk to the patient. OR
--will be undergoing a procedure due to medical necessity during which the tissue may be collected OR
--tissue blocks collected within 6 mo prior to pre-reg are available for a patient who has not received any intervening therapy that is considered to be targeted- the patient may have received cytoxic chemo for up to 4 cycles but must not have responded
-Patient must not require the use of full dose coumadin-derivative anticoagulants such as warfarin. Low molecular weight heparin is permitted for prophylactic or therapeutic use. Factor X inhibitors are permitted.
-Patients must have ECOG performance status 0- 1
-Any prior therapy, radiotherapy (except palliative radiation therapy of 30 Gy or less), or major surgery must have been completed greater than or equal to 4 weeks prior to treatment on MATCH and patient must be recovered from adverse events due to prior therapy (except alopecia and lymphopenia)
-Palliative radiation therapy must have been completed at least 2 weeks prior to enrollment on a MATCH treatment arm and patient must have recovered from any adverse events of this therapy.
-Patients with brain metastases or primary brain tumors must have completed treatment, surgery or radiation therapy greater than or equal to 4 weeks prior to registration.
-NOTE: patients may receive non-protocol treatment after biopsy until they receive notification of results as specified per protocol; however, patients will need to be off of therapy for at least 4 weeks before receiving MATCH treatment.
-Patients with brain mets or primary brain tumors must have completed tx, surgery or RT at least 4 weeks prior to tx.
-Patients must have discontinued steroids greater than or equal to 1 week prior to registration (see protocol for exceptions). Patients with glioblastoma (GBM) must have been on stable dose of steroids, or be off steroids, for one week prior to registration
-No factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age or any concomitant medication known to prolong the QT interval

Step 1 Eligibility:

-See the specific subprotocol eligibility
-Some patients may be eligible to have their results rerun in Matchbox, even if they did not match to a treatment initially. See protocol for details.

Step 2 Eligibility:
-Patient's disease has progressed on Step 1 treatment or could not tolerate assigned treatment.
-Patients must meet one of the following criteria:
--No response and progression occurred less than 6 months from start of Step 1 treatment AND the MATCH assay results (received during Step 0) indicated > 1 targeted treatment.
--Progression occurred after a (1) response OR (2) after greater than or equal to 6 months from start of Step 1 treatment. 
-Patients must meet eligibility criteria for biopsy

Patient can be registered to subsequent steps depending on eligibility for further subprotocols.

Subprotocol E Eligibility (in addition to master):
-Patients must have either:
--Any malignancy other than non-small cell lung cancer and have EGFR T790M identified in their tumor, with or without an activating mutation OR
--Any malignancy harboring any of the following mutations: EGFR G719A, G719C, G719D, G719S EGFR L861Q, S786I or an EGFR exon 19 in frame insertion mutation
-Patients must have an ECG within 8 weeks prior to treatment assignment and must have no clinically important abnormalities in rhythm, conduction or morphology of resting ECG .
-Patients must have an ECHO/MUGA within 4 weeks prior to treatment assignment and must not have a LVEF < institutional LLN.
-Patients must not have known hypersensitivity to AZD9291 or compounds of similar chemical or biologic composition.
-Patient must not have received AZD9291, WZ4002, CO-1686, HM61713, EGF816 or ASP8273 previously.
-Patients known to harbor germline EGFR T790M mutations are excluded from the study. Prospective testing for germline mutations is not required.

Subprotocol F Eligibility (in addition to master):
-Patients must have an ALK rearrangement as determined by the MATCH screening assessment.
-Patients must not have non small cell lung cancer or ALCL.
-Patients with a history of interstitial lung disease or pneumonitis are excluded.
-Patients must have an ECG within 8 weeks prior to treatment assignment and must have no clinically important abnormalities in rhythm, conduction or morphology of resting ECG
-Patients must not have known hypersensitivity to crizotinib or compounds of similar chemical or biologic composition.
-Patients must not have had prior ALK-targeted inhibitors, including crizotinib, ceritinib, alectinib, AP26113, TSR-011, X-396, RXDX-101, CEP-37440, PF-06463922Patients must not have had brain metastases unless 1) treated and neurologically stable for at least 2 weeks, or 2) untreated, asymptomatic, and treatment is not indicated. Steroids are permitted if doses are stable (or tapering) for 2 weeks prior to study enrollment.

Subprotocol G Eligibility (in addition to master):
-Patients must be positive for translocation or inversion events involving the ROS1 gene as detected on the MATCH NGS assay
-Patients must not have adenocarcinoma of the lung.
-Patients with a history of interstitial lung disease or pneumonitis are excluded.
-Patients must have an electrocardiogram (ECG) within 8 weeks prior to treatment assignment and must have no clinically important abnormalities in rhythm, conduction or morphology of resting ECG
-Patients must not have known hypersensitivity to crizotinib or compounds of similar chemical or biologic composition.
-Patients must not have had prior therapy with any ROS1 inhibitor including crizotinib, ceritinib, foretinib, cabozantinib, AP26113, ASP3026, WZ-5-126, TAE684, KIST301072, KIST301080, AZD1480, PF-06463922, RXDX-101 and PF-3922

Subprotocol H Eligibility (in addition to master)
-Patients must have a BRAF V600E or, V600K, V600R or V600D mutation as identified via the MATCH Master Protocol.
-Patients with a diagnosis of metastatic melanoma from a cutaneous, acral, mucosal, or unknown primary site are excluded.
-Patients with a diagnosis of papillary thyroid cancer are excluded.
-Patients with a diagnosis of colorectal cancer are excluded
-Patients must have an ECHO/MUGA within 4 weeks prior to treatment assignment and must not have a LVEF < the institutional LLN.
-Patients must have an electrocardiogram (ECG) within 8 weeks prior to treatment assignment and must have NONE of the following cardiac criteria:
--Clinically important abnormalities in rhythm, conduction or morphology of resting ECG (e.g. complete left bundle branch block, third degree heart block).
--Treatment-refractory hypertension defined as a blood pressure of systolic >140 mmHg and/or diastolic > 90 mmHg which cannot be controlled by anti-hypertensive therapy.
-Patients with a history of interstitial lung disease or pneumonitis are excluded.
-Patients must not have known hypersensitivity to dabrafenib and trametinib or compounds of similar chemical or biologic composition or to dimethyl sulfoxide (DMSO).
-Patients must not have a history or current evidence/risk of retinal vein occlusion (RVO). 
-Patients who previously received MEK inhibitors (including, but not limited to, trametinib, binimetinib, cobimetinib, selumetinib, RO4987655 (CH4987655), GDC-0623 and pimasertib) will be excluded.
-Patients who previously received BRAF inhibitors (including, but not limited to, dabrafenib (Tafinlar), vemurafenib (PLX-4720) (Zelboraf), RAF265, LGX818 (encorafenib), RO5212054 (PLX3603), ARQ 736, XL281 (BMS-908662), CEP-32496, and the BRAF/MEK dual inhibitor RO5126766) will be excluded.
-Patients with prior exposure to dabrafenib or trametinib on another treatment subprotocol of the MATCH trial are excluded.
-Patients who previously received monoclonal antibody therapy (eg. Ipilimumab and others) must have stopped the prior therapy for 8 or more weeks before starting on trametinib and dabrafenib.
-Patients with a history of Hepatitis B Virus (HBV) or Hepatitis C Virus (HCV) infection are excluded.
-Patients with history of RAS mutation-positive tumors are not eligible regardless of interval from the current study.